Day: October 11, 2022

Cheng, Gang; Pan, Jing; Podsiadly, Radoslaw; Zielonka, Jacek; Garces, Alexander M.; Dias Duarte Machado, Luiz Gabriel; Bennett, Brian; McAllister, Donna; Dwinell, Michael B.; You, Ming; Kalyanaraman, Balaraman published the artcile< Increased formation of reactive oxygen species during tumor growth: Ex vivo low-temperature EPR and in vivo bioluminescence analyses>, Computed Properties of 2591-17-5, the main research area is ROS tumor growth bioluminescence analysis boronate proluciferin probe ESR; Bioluminescence; EPR; Mitochondria; Oxidants; Tumor growth.

Previous studies have shown that reactive oxygen species (ROS) such as superoxide or hydrogen peroxide generated at low levels can exert a tumor-promoting role via a redox-signaling mechanism. Reports also suggest that both tumorigenesis and tumor growth are associated with enhanced ROS formation. However, whether ROS levels or ROS-derived oxidative marker levels increase during tumor growth remains unknown. In this study, in vivo bioluminescence imaging with a boronate-based pro-luciferin probe was used to assess ROS formation. Addnl., probe-free cryogenic ESR was used to quantify a characteristic aconitase [3Fe4S]+ center that arises in the tumor tissue of mouse xenografts from the reaction of the native [4Fe4S]2+ cluster with superoxide. Results indicated that tumor growth is accompanied by increased ROS formation, and revealed differences in oxidant formation in the inner and outer sections of tumor tissue, resp., demonstrating redox heterogeneity. Studies using luciferin and pro-luciferin probes enabled the assessment of tumor size, ROS formation, and bioenergetic status (e.g., ATP) in luciferase-transfected mice tumor xenografts. Probe-free ex vivo low-temperature ESR can also be translated to clin. studies.

Free Radical Biology & Medicine published new progress about Animal cell line (H2030). 2591-17-5 belongs to class thiazole, and the molecular formula is C11H8N2O3S2, Computed Properties of 2591-17-5.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Sartori, Luca; Mercurio, Ciro; Amigoni, Federica; Cappa, Anna; Faga, Giovanni; Fattori, Raimondo; Legnaghi, Elena; Ciossani, Giuseppe; Mattevi, Andrea; Meroni, Giuseppe; Moretti, Loris; Cecatiello, Valentina; Pasqualato, Sebastiano; Romussi, Alessia; Thaler, Florian; Trifiro, Paolo; Villa, Manuela; Vultaggio, Stefania; Botrugno, Oronza A.; Dessanti, Paola; Minucci, Saverio; Zagarri, Elisa; Carettoni, Daniele; Iuzzolino, Lucia; Varasi, Mario; Vianello, Paola published the artcile< Thieno[3,2-b]pyrrole-5-carboxamides as New Reversible Inhibitors of Histone Lysine Demethylase KDM1A/LSD1. Part 1: High-Throughput Screening and Preliminary Exploration>, Application In Synthesis of 1003-32-3, the main research area is thienopyrrolecarboxamide preparation histone lysine demethylase KDM1A inhibitor screening.

Lysine specific demethylase 1 KDM1A (LSD1) is one regulator of histone methylation and it is increasingly recognized as a potential therapeutic target in oncol. The authors report on a high-throughput screening campaign performed on KDM1A/CoREST, using a time resolved fluorescence resonance energy transfer (TR-FRET) technol., to identify reversible inhibitors. The screening led to 115 hits for which the authors determined biochem. IC50, thus identifying 4 chem. series. After data anal., the authors have prioritized the chem. series of N-phenyl-4H-thieno[3,2-b]pyrrole-5-carboxamide for which the authors obtained x-ray structures of the most potent hit (compound 19, IC50 = 2.9 μM) in complex with the enzyme. Initial expansion of this chem. class, both modifying core structure and decorating benzamide moiety, was directed towards the definition of the moieties responsible for the interaction with the enzyme. Preliminary optimization brought to compound 90 (4-methyl-N-[3-[[4-(4-piperidyloxy)phenoxy]methyl]phenyl]- thieno[3,2-b]pyrrole-5-carboxamide) which inhibited the enzyme with a submicromolar IC50 (0.162 μM), capable to inhibit the target in cells.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Application In Synthesis of 1003-32-3.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Bataille, Carole J. R.; Brennan, Meabh B.; Byrne, Simon; Davies, Stephen G.; Durbin, Matthew; Fedorov, Oleg; Huber, Kilian V. M.; Jones, Alan M.; Knapp, Stefan; Liu, Gu; Nadali, Anna; Quevedo, Camilo E.; Russell, Angela J.; Walker, Roderick G.; Westwood, Robert; Wynne, Graham M. published the artcile< Thiazolidine derivatives as potent and selective inhibitors of the PIM kinase family>, SDS of cas: 1003-32-3, the main research area is thiazolidine preparation serine threonine kinase inhibitor anticancer agent; Knoevenagel condensation Sukuki coupling; Anti-cancer; High throughput screen; Kinase inhibitor; PIM kinase; Thiazolidine.

The PIM family of serine/threonine kinases have become an attractive target for anti-cancer drug development, particularly for certain hematol. malignancies. Here, we describe the discovery of a series of inhibitors of the PIM kinase family using a high throughput screening strategy. Through a combination of mol. modeling and optimization studies, the intrinsic potencies and mol. properties of this series of compounds was significantly improved. An excellent pan-PIM isoform inhibition profile was observed across the series, while optimized examples show good selectivity over other kinases. Two PIM-expressing leukemic cancer cell lines, MV4-11 and K562, were employed to evaluate the in vitro anti-proliferative effects of selected inhibitors. Encouraging activities were observed for many examples, with the best example (44) giving an IC50 of 0.75 μM against the K562 cell line. These data provide a promising starting point for further development of this series as a new cancer therapy through PIM kinase inhibition.

Bioorganic & Medicinal Chemistry published new progress about Aldehydes Role: RCT (Reactant), RACT (Reactant or Reagent). 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, SDS of cas: 1003-32-3.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Zhang, Ru; He, Jinwu; Dong, Zhiwei; Liu, Guichun; Yin, Yuan; Zhang, Xinying; Li, Qi; Ren, Yandong; Yang, Yongzhi; Liu, Wei; Chen, Xianqing; Xia, Wenhao; Duan, Kang; Hao, Fei; Lin, Zeshan; Yang, Jie; Chang, Zhou; Zhao, Ruoping; Wan, Wenting; Lu, Sihan; Peng, Yanqiong; Ge, Siqin; Wang, Wen; Li, Xueyan published the artcile< Genomic and experimental data provide new insights into luciferin biosynthesis and bioluminescence evolution in fireflies>, Recommanded Product: (S)-2-(6-Hydroxybenzo[d]thiazol-2-yl)-4,5-dihydrothiazole-4-carboxylic acid, the main research area is Lamprigera luciferin bioluminescence evolution.

Abstract: Fireflies are among the most charismatic insects for their spectacular bioluminescence, but the origin and evolution of bioluminescence remain elusive. Especially, the genic basis of luciferin (D-luciferin) biosynthesis and light patterns is largely unknown. Here, we present the high-quality reference genomes of two fireflies Lamprigera yunnana (1053 Mb) and Abscondita terminalis (501 Mb) with great differences in both morphol. and luminous behavior. We sequenced the transcriptomes and proteomes of luminous organs of two species. We created the CRISPR/Cas9-induced mutants of Abdominal B gene without luminous organs in the larvae of A. terminalis and sequenced the transcriptomes of mutants and wild-types. Combining gene expression analyses with comparative genomics, we propose a more complete luciferin synthesis pathway, and confirm the convergent evolution of bioluminescence in insects. Using experiments, the function of the firefly acyl-CoA thioesterase (ACOT1) to convert L-luciferin to D-luciferin was validated for the first time. Comparisons of three-dimension reconstruction of luminous organs and their differentially expressed genes among two species suggest that two pos. genes in the calcium signaling pathway and structural difference of luminous organs may play an important role in the evolution of flash pattern. Altogether, our results provide important resources for further exploring bioluminescence in insects.

Scientific Reports published new progress about Aquatica lateralis. 2591-17-5 belongs to class thiazole, and the molecular formula is C11H8N2O3S2, Recommanded Product: (S)-2-(6-Hydroxybenzo[d]thiazol-2-yl)-4,5-dihydrothiazole-4-carboxylic acid.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Ling, Xing; Lu, Weiwei; Miao, Lin; Marcaurelle, Lisa A.; Wang, Xuan; Ding, Yun; Lu, Xiaojie published the artcile< Divergent On-DNA Transformations from DNA-Linked Piperidones>, Quality Control of 1003-32-3, the main research area is DNA linked heterocycle preparation.

A group of highly efficient and divergent transformations for constructing multiple DNA-linked chemotypes based on piperidones e.g., I core is successfully developed. The first procedure for the synthesis of DNA-conjugated piperidines II (R = H, Bn, (4-cyanophenyl)methyl, (3,4,5-trifluorophenyl)methyl, etc.; R1 = 2,2-dimethoxyethyl, Bn, 3-cyclohexylpropanoyl, etc.) intermediate under basic conditions was reported. Subsequently, this substructure was subjected to addnl. reactions to generate several privileged scaffolds, including 4-aminopiperidines II, fused [1,2,4]triazolo[1,5-a]pyrimidines III (R2 = methanesulfonyl, (3-fluorophenyl)methyl, benzenesulfonamido), and a quinoline derivative e.g., IV. These transformations paved the way for constructing focused scaffold-based DNA-encoded libraries with druglike properties.

Journal of Organic Chemistry published new progress about Acids Role: RCT (Reactant), RACT (Reactant or Reagent). 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Quality Control of 1003-32-3.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Villa, Reymundo; Mandel, Alexander L.; Jones, Brian D.; La Clair, James J.; Burkart, Michael D. published the artcile< Structure of FD-895 Revealed through Total Synthesis>, Recommanded Product: (S)-4-Benzylthiazolidine-2-thione, the main research area is FD895 synthesis structure antitumor.

The total synthesis of FD-895 (I) was completed through a strategy that featured the use of a tandem esterification ring-closing metathesis (RCM) process to construct the 12-membered macrolide and a modified Stille coupling to append the side chain. These studies combined with detailed anal. of all four possible C16-C17 stereoisomers were used to confirm the structure of FD-895 and identify an analog with an enhanced subnanomolar bioactivity.

Organic Letters published new progress about Absolute configuration. 171877-39-7 belongs to class thiazole, and the molecular formula is C10H11NS2, Recommanded Product: (S)-4-Benzylthiazolidine-2-thione.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Yu, Mohan; Liu, Yajun published the artcile< A QM/MM Study on the Initiation Reaction of Firefly Bioluminescence-Enzymatic Oxidation of Luciferin>, Application In Synthesis of 2591-17-5, the main research area is luciferin bioluminescence enzymic oxidation quantum mol mechanic study; QM/MM; firefly bioluminescence; luciferin oxidation; mechanism; single electron transfer.

Among all bioluminescent organisms, the firefly is the most famous, with a high luminescent efficiency of 41%, which is widely used in the fields of biotechnol., biomedicine and so on. The entire bioluminescence (BL) process involves a series of complicated in-vivo chem. reactions. The BL is initiated by the enzymic oxidation of luciferin (LH2). However, the mechanism of the efficient spin-forbidden oxygenation is far from being totally understood. Via MD simulation and QM/MM calculations, this article describes the complete process of oxygenation in real protein. The oxygenation of luciferin is initiated by a single electron transfer from the trivalent anionic LH2 (L3-) to O2 to form 1[L•2-…O2•-]; the entire reaction is carried out along the ground-state potential energy surface to produce the dioxetanone (FDO-) via three transition states and two intermediates. The low energy barriers of the oxygenation reaction and biradical annihilation involved in the reaction explain this spin-forbidden reaction with high efficiency. This study is helpful for understanding the BL initiation of fireflies and the other oxygen-dependent bioluminescent organisms.

Molecules published new progress about Annihilation radiation. 2591-17-5 belongs to class thiazole, and the molecular formula is C11H8N2O3S2, Application In Synthesis of 2591-17-5.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Stress, Cedric J.; Sauter, Basilius; Schneider, Lukas A.; Sharpe, Timothy; Gillingham, Dennis published the artcile< A DNA-Encoded Chemical Library Incorporating Elements of Natural Macrocycles>, Quality Control of 96929-05-4, the main research area is DNA encoded library macrocycle compound; DNA chemistry; DNA-encoded libraries; Lipinski rules; chemical libraries; macrocycles.

Here the authors show a seven-step chem. synthesis of a DNA-encoded macrocycle library (DEML) on DNA. Inspired by polyketide and mixed peptide-polyketide natural products, the library was designed to incorporate rich backbone diversity. Achieving this diversity, however, comes at the cost of the custom synthesis of bifunctional building block libraries. This study outlines the importance of careful retrosynthetic design in DNA-encoded libraries, while revealing areas where new DNA synthetic methods are needed.

Angewandte Chemie, International Edition published new progress about Combinatorial library (DNA-encoded). 96929-05-4 belongs to class thiazole, and the molecular formula is C12H18N2O4S, Quality Control of 96929-05-4.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Wu, Yue-Xiao; Peng, Kang; Hu, Zhi-Chao; Fan, Yong-Hao; Shi, Zhen; Hao, Er-Jun; Dong, Zhi-Bing published the artcile< Iodine-Mediated Cross-Dehydrogenative Coupling of Heterocyclic Thiols with Amines: An Easy and Practical Formation of S-N Bond>, Synthetic Route of 96-53-7, the main research area is amine heteroaryl thiol iodine promoter cross dehydrogenative coupling; heteroaryl sulfenamide preparation.

An efficient iodine-mediated construction of S-N bond was developed. Such a cross-dehydrogenative coupling of heterocyclic thiols with amines proceeded smoothly under metal-free and base-free conditions, and afforded a series of sulfenamides in good to excellent yields. The easily available substrates and convenient synthetic procedure illustrate potential synthetic value of this protocol for the preparation of sulfenamide related biol. or pharmaceutically active compounds

European Journal of Organic Chemistry published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 96-53-7 belongs to class thiazole, and the molecular formula is C3H5NS2, Synthetic Route of 96-53-7.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Mercadante, Dayna L.; Manning, Amity L.; Olson, Sarah D. published the artcile< Modeling reveals cortical dynein-dependent fluctuations in bipolar spindle length>, Formula: C22H23F2N3O2S, the main research area is cortical dynein bipolar spindle mitosis.

Proper formation and maintenance of the mitotic spindle is required for faithful cell division. Although much work has been done to understand the roles of the key mol. components of the mitotic spindle, identifying the consequences of force perturbations in the spindle remains a challenge. We develop a computational framework accounting for the minimal force requirements of mitotic progression. To reflect early spindle formation, we model microtubule dynamics and interactions with major force-generating motors, excluding chromosome interactions that dominate later in mitosis. We directly integrate our exptl. data to define and validate the model. We then use simulations to analyze individual force components over time and their relationship to spindle dynamics, making it distinct from previously published models. We show through both model predictions and biol. manipulation that rather than achieving and maintaining a constant bipolar spindle length, fluctuations in pole-to-pole distance occur that coincide with microtubule binding and force generation by cortical dynein. Our model further predicts that high dynein activity is required for spindle bipolarity when kinesin-14 (HSET) activity is also high. To the best of our knowledge, our results provide novel insight into the role of cortical dynein in the regulation of spindle bipolarity.

Biophysical Journal published new progress about Cell division. 2222768-84-3 belongs to class thiazole, and the molecular formula is C22H23F2N3O2S, Formula: C22H23F2N3O2S.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica